Trajectories of α-fetoprotein and unresectable hepatocellular carcinoma outcomes receiving lenvatinib: a retrospective, multicenter cohort study.

BACKGROUND

Dynamic changes in alpha-fetoprotein (AFP) levels may serve as biomarkers for systemic therapy response in hepatocellular carcinoma (HCC). This study investigates the AFP trajectories in patients receiving lenvatinib treatment and their relationship with survival.

MATERIALS AND METHODS

A retrospective analysis was conducted on 553 patients diagnosed with unresectable hepatocellular carcinoma (uHCC) who received lenvatinib as a first-line systemic treatment at four centers between March 2019 and March 2022. The latent class linear mixed model was used to fit the dynamic changes of AFP and generate AFP trajectories. Multivariable Cox models were utilized to calculate hazard ratios (HRs) for survival. The primary endpoint was overall survival (OS), while the secondary endpoint was progression-free survival (PFS).

RESULTS

Four distinct AFP trajectories were identified among patients with unresectable HCC: High-stable (n = 100), High-rising (n = 91), Sharp-falling (n = 117), and Low-stable (n = 245). Using the High-stable group as the reference, no statistically significant differences in OS and PFS were observed for the High-rising group. However, the Sharp-falling and Low-stable groups exhibited a reduced risk of death, with HRs of 0.28 (95% CI: 0.18-0.42, p < 0.001) and 0.42 (95% CI: 0.25-0.71, p = 0.001), respectively. Similarly, the risk of disease progression was lower in these groups, with HRs of 0.34 (95% CI: 0.24-0.47, p < 0.001) and 0.36 (95% CI: 0.23-0.55, p < 0.001), respectively.

CONCLUSION

Four distinct AFP trajectories exist in uHCC patients receiving lenvatinib, serving as independent biomarkers for clinical outcomes. AFP trajectories provide valuable biomarkers for assessing treatment efficacy and optimizing therapeutic strategies.